Efficient separation of suspended particles and cells is essential to many fundamental biomedical studies such as cancer cell detection and drug screening. The most popular methods for cell separation in the life science laboratory so far are the centrifugal methods, which are capable of separating cells with differences in size and density. Another industrial and clinical standard for high quality cell separation is a FACS (fluorescence activated cell sorter). The FACS technology is performed in a sheath flow mode where cells are focused in the center of buffer and then pass through a laser beam for high speed and precise optical detection. The cells can be separated by a downstream electric field triggered by the optical signal. In the past years, fundamental advances in the lab-on-a-chip technologies have driven development of new approaches to cell separation. Examples include magnetic, hydrodynamic, optical lattice, electrophoresis/dielectrophoretic (DEP), and acoustic methods.
The magnetic method starts with labeling cells of interest with magnetic markers. Then an external magnetic field is applied to the sample, leading to the separation of labeled cells from the rest. The labeling step required for magnetic methods usually increases cost and processing time, and may also have a negative effect on the cells of interest. The hydrodynamic methods usually involve high flow speed (inertial force based method) or asymmetric obstacles inside the channel (deterministic lateral displacement). These methods permit continuous operation without requiring additional labeling or external forces. However, the channel obstacles in the channel may exert high mechanical stress on cells and lead to low throughput. The optical lattice method provides a unique separation approach which can separate particles with different optical properties. However, this approach has two potential shortcomings: 1) the potential laser-induced heating, the formation of singlet oxygen, and multiphoton absorption in biological materials may cause physiological damage to cells and other biological objects; and 2) the method relies on complex, potentially expensive optical setups that are difficult to maintain and miniaturize. Electrophoresis/dielectrophoresis based methods are strictly dependent on particle polarizibility and medium conductivity, and utilize electrical forces that may adversely affect cell physiology due to current-induced heating and/or direct electric-field interaction.
Acoustic-based particle manipulation methods present excellent alternatives. Compared to their optical, electrical, or magnetic counterparts, acoustic-based methods are relatively non-invasive to biological objects and work for most microparticles regardless of their optical, electrical, or magnetic properties. The well developed bulk acoustic wave (BAW) acoustophoresis has demonstrated the separation of cells based on size and density in microfluidic chips without any labeling on the target particles or cells. This BAW method, however, requires a channel material with excellent acoustic reflection properties (such as silicon and glass). The widely used soft polymer materials in microfluidic applications, such as PDMS, usually do not have those properties. Moreover, the transducer to generate BAW is bulky and hinders the system integration and miniaturization.